Transcript Document
Contrast Induced Nephropathy
Saudi Arabia Cardiac Interventional Society Society of Cardiovascular Angiography and Intervention (SCAI) Arabia Fellow’s Course
April 10, 2014
Charles E. Chambers, MD, FSCAI, FACC, NCRP President Elect, SCAI Professor of Medicine and Radiology Pennsylvania State University College of Medicine Director, Cardiac Catheterization Laboratories MS Hershey Medical Center, Hershey, PA
How to Minimize Radiographic Contrast Reactions: Anaphylactoid & Acute Renal Injury
Society for Cardiovascular Angiography and Intervention Mission Statement SCAI promotes excellence in invasive and interventional cardiovascular medicine through physician education and representation, and the advancement of quality standards to enhance patient care.
Radiographic Contrast Media
History
First introduced in 1923 (SrBr) to study the urinary tract, with NaI introduced in 1924.
RCM makes fluid visible by increasing x-ray (60-125 photon kVp) absorbance based on elemental atomic number and density with iodine best.
Minimum iodine concentrations are 300 mg/ml (normal range 320-400 mg/dl).
Classification is based upon an agents ability to dissociate (ionic) or not dissociate (nonionic) into ionic particles when introduced into blood.
Criteria for “Ideal” Radiographic Contrast Media
Must be liquid at room temperature with viscosity similar to blood.
It must contain an element with sufficiently high atomic number in a concentration adequate to provide an x-ray absorbance that is 10 percent greater than blood .
It’s components must be biocompatible, with the lowest side effect profile, and easily eliminated from the body .
Hirshfeld JW. Radiographic Contrast Agents. In Cardiac Imaging, ed Marcus, Schelbert, Skorton, Wolf, 1991
Radiographic Contrast Media
Classification is based upon the agent’s ability to dissociate (ionic) or not dissociate (nonionic) into ionic particles Ionic Dimer Ionic Monomer Nonionic Monomer Nonionic Dimer
Radiographic Contrast Media
Product Type I Concentration Osmolality (mgI/mL) (mOsm/kg H 2 O)
---------------------------------------------------------------------------------------------------------
Monomers
iohexol (Omnipaque) non-ionic 350 844 iopamidol (Isovue) ioxilan (Oxilan) iopromide (Ultravist) ioversol (Optiray) non-ionic non-ionic non-ionic non-ionic 370 350 370 350 796 695 774 792
Dimers
iodixanol (Visipaque) ioxaglate (Hexabrix)
__
non-ionic ionic 320 320 290 600
Kozak M, Chambers, CE. Cardiac Catheterization Laboratory: In: Kaplan, JA, ed. Kaplan's Cardiac Anesthesia. 6th ed., 2011
“Allergic” Reactions to RCM
Differentiate Chemotoxic from Anaphylactoid Anaphylactoid not anaphylactic since non-IgE medicated , therefore no skin tests are available or invitro tests to detect potential allergic rxns Allergy to “fish” is unrelated to RCM allergy since the presence of iodine in fish and contrast media is not a common antigenic factor.
A trial administration detect of a small dose of contrast may well not potential reactions to the therapeutic dose.
Incidence of Repeat Anaphylactoid Contrast Reactions Without prophylaxis- 44% With steroid and diphenhydramine-5% With steroids, diphenhydramine, and non-ionic contrast-0.5% Reisman RE. Anaphylaxis, in Allergy and Immunology, AM Coll of Physicians, 1998
Anaphylactoid Reaction Prophylaxis
Prednisone : 50 mg po 6pm, midnight, and 6 AM prior to catheterization.
Most important dose likely the one >12 hrs prior.
Diphenhydramine : 50mg, given IV on call Non-ionic contrast used.
Limited role for H 2 blockers and ephedrine.
Should not use H 2 without H 1 .
Ephedrine not proven beneficial in the cardiac pt.
Emergent procedures, limited data: Hydrocortisone, 200 mg IV q 4 hrs, until procedure .
Goss JE, Chambers CE, Heupler. Systemic Anaphylactoid Rxns to RCM/ CCD 1995. 34: 88-104.
Therapy for Anaphylactoid Reactions
Minor-Uticaria, with or without Skin Itching
No therapy Diphenhydramine, 25-50mg IV Epinephrine 0.3 cc of 1:1,000 solution sub Q q 15 min up to 1 cc Cimetadine 300 mg or ranitadine 50 mg in 20 cc NS IV over 15 mins
Facial/Laryngeal Edema
Call anesthesia Assess airway O2 mask, Intubation, Tracheostomy tray Mild-Epinephrine sq Moderate/Severe: Epi-IV 0.3 cc of 1:1,000 solution sub-Q q 15 min, 1 cc Diphenhydramine 50 mg IV Hydrocortisone 200-400 mg IV Optional: H2 blocker
Bronchosapsm
Oxygen Mild- albuterol inhaler, 2 puffs Moderate-Epinephrine 0.3 cc of 1:1,000 sub-Q up to 1 cc Severe-Epinephrine IV as bolus 10 micrograms/min then infusion 1 to 4 micrograms/min Diphenhydramine 50 mg IV Hydrocortisone 200-400mg IV Consider H2 blocker
Hypotension/Shock
Epinephrine IV boluses Large volumes 0.9% NS (1-3 l) CVP, PA catheter Airway, intubation as needed Diphenhydramine 50 mg IV Hydrocortisone 400mg IV If unresponsive… H2 blocker Dopamine/nor epinephrine
2011 PCI Guidelines 3.3 Anaphylactoid Reactions Recommendations
Class I 1. Patients with prior evidence of an anaphylactoid reaction to contrast media should receive appropriate steroid and antihistamine prophylaxis prior to repeat contrast administration . (Level of Evidence B)
Class III: No Benefit 1. In patients with prior history of allergic reactions to shellfish or seafood, anaphylactoid prophylaxis for contrast reaction is not beneficial. (Level of Evidence: C)
Delayed Contrast Reaction
Uncommon Exclude Clopidogrel Other drugs Consider Steroids Other Dx.
Contrast Injury to the Kidney
Contrast Induced Nephropathy (CIN) Acute Kidney Injury AKIN /KDIGO Classification
Definition: 0.5 mg/dl.
an increase in serum Cr from baseline of >25%, or absolute >0.25 or Baseline renal disease increases risk as assessed by eGFR or CrCl; age, sex , and obesity factors in estimating eGFR/CrCl.
Renal dysfunction is identifiable by 48 hrs most often returns to baseline by 7-10 days.
and Stage 1 1.5 to 1.9 fold increase in Cr Absolute increase >0.3 mg/dl Stage 2 2-2.9 fold increase in Cr Stage 3 >3 fold increase in serum Cr Absolute increase >4 mg/dl Acute increase >0.5 mg/dl AKIN-Acute Kidney Injury Network KDIGO-Kidney Disease: Improvement in Global Outcomes
Acute Kidney Injury from Contrast
NCDR Report Incidence/Predictors Outcomes (In-hospital)
985,737 patients underwent PCI at 1,253 sites from June 2009- June 2011with AKIN criteria No AKI MI-2.1% Bleeding -1.4% Death-0.5% Overall Incidence 7.1% with: AKI MI-3.8% Stage 1-6.0%; stage 2-0.5%; stage 3-0.3% ; dialysis 0.3% Bleeding -6.4% Predictors Death-9.6% Dialysis STEMI MI -7.9% Cardiogenic shock Bleeding -15.8% Pre-existent renal disease Death-34.3% Contrast volume Tsai et al. Contemporary Incidence, Predictors, and Outcomes of AKI in pts undergoing PCI. JACC Interv. 2014 Vol7 #1; Pg 1-9.
Pre-procedural Clinical Risk Factors for Contrast Induced Nephropathy
Modifiable Risk Factors
Contrast volume Hydration status Concomitant nephrotoxic agents Recent contrast administrations
Non-modifiable Risk Factors
Diabetes/Chronic kidney disease Shock/hypotension Advanced age (> 75 yrs) Advanced congestive heart failure Klein LW, Sheldon MA, Brinker J, Mixon TA, Skeldiong K, Strunk AO, Tommaso CL, Weiner B, Bailey SR, Uretsky B, Kern M, Laskey W . The use of radiographic contrast media during PCI: A focused review. Cathet Cardiovasc Int 2009; 74: 728-46
Multi-factorial Predictors of CIN
Variable Score Hypotension 5 IABP use CHF 5 5 Odds Ratio 2.537
2.438
2.250
SCR>1.5
Age.75
Anemia DM 4 4 3 3 2.053
1.847
1.601
1.508
Contrast Volume 1/100 1.290
P Value <0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
Mehran R J. Am Coll Cardiolo. 2004;44:1393-99.
Multi-factorial Predictors of CIN
Clinical Features of CIN
Oliguria rare Urinalysis Nonspecific findings including red cell/granular casts Mild proteinuria Fractional Excretion of Na May be <1% Exclude Other Causes Cholesterol emboli
Non- RCM Related Procedural Complications Resulting In Renal Injury
Cholesterol Emboli Renal Insufficiency identified week(s) later Livedo reticularis Necrotic toes Eosinophilia Crystals on bx
Cholesterol Emboli
Cardiac Complication in Patients with CIN Post PCI
Mayo Clinic Registry of 7,586 pts post PCI Patients with CIN had increased rates of:
CABG
Q-MI
CK Rise
Low BP
Shock
Cardiac Arrest p=0.004
p< 0.001
p<0.001
p<0.001
p<0.001
p<0.001
Rihal CS. Circ. 2002; 105:2259-64.
Mortality with CIN
Acute Kidney Injury from Contrast
NCDR Report Incidence/Predictors Outcomes (In-hospital)
985,737 patients underwent PCI at 1,253 sites from June 2009- June 2011with AKIN criteria No AKI MI-2.1% Bleeding -1.4% Death-0.5% Overall Incidence 7.1% with: AKI MI-3.8% Stage 1-6.0%; stage 2-0.5%; stage 3-0.3% ; dialysis 0.3% Bleeding -6.4% Predictors Death-9.6% Dialysis STEMI MI -7.9% Cardiogenic shock Bleeding -15.8% Pre-existent renal disease Death-34.3% Contrast volume Tsai et al. Contemporary Incidence, Predictors, and Outcomes of AKI in pts undergoing PCI. JACC Interv. 2014 Vol7 #1; Pg 1-9.
Reducing CIN Risk
Not Prevention
Identify Risk
Low risk:
eGFR > 60 ml/1.73 m2 Optimize hydration status.
High risk:
eGFR <60 ml/1.73 m2 Schedule outpatient for early arrival and/or delay procedure time to allow time to accomplish the hydration.
Pre-Procedure
Hydration Normal Saline preferred over D5 ½ normal; IV not oral Sodium Bicarbonate, mixed reviews Medications NSAID stop if possible N-acetylcysteine, mixed reviews, no clear benefit Statins (+/_); theophyline (-)
Procedure
Contrast to CrCl ratio Contrast Volume, repeat studies Type-non-ionic/isoosmolar
Post Procedure
Hydration: Normal Saline & PO
2011 PCI Guidelines 3.2 Contrast-Induced Acute Kidney Injury Recommendations
Class I 1. Patients should be assessed for risk of contrast-induced AKI before PCI. (Level of Evidence: C) 2. Patients undergoing cardiac catheterization with contrast media should receive adequate preparatory hydration . (Level of Evidence: B) 3. In patients with chronic kidney disease (creatinine clearance <60cc/min), the volume of contrast media should be minimized . (Level of Evidence: B) Class III: No Benefit 1. Administration of N-acetyl-L-cysteine is not useful for the prevention of contrast induced AKI . (Level of Evidence: A )
Contrast Dose
Maximal Allowable Contrast Dose (MACD) 5 cc contrast x body wgt (kg)/ baseline Cr Brown et al, Circ Interv, 2010.
Volume to Creatinine Clearance Ratio Contrast volume/ CrCl Laskey, JACC 2007, unselected population, 3.7 ratio Gurm et al, JACC, 2011, <2 safe; >3 concern
Contrast Type
Low osmolar or Iso-osmolar better than high osmolar contrast Iso-osmolar may be better than certain low osmolar contrast (iohexol) but has not consistently been proven for all low osmolar agents.
Keys Low-osmolar
or
iso-osmolar Limit dose Repeat studies>72 hrs, if clinically possible
• • •
Design
CARE
482 patients enrolled between July 2005 and June 2006 in 25 clinical site in North America DESIGN: Prospective, randomized, double-blind, parallel-group, multi-center clinical evaluation ipamidol-370 and iodixanol-320 OBJECTIVE: 320 To compare the incidence of CIN between iopamidol-370 and iodixanol 468 assigned to a treatment arm 230 patients assigned to Iopamidol-370 14 patients withdrew consent 236 patients assigned to Iodixanol-320 26 excluded 26 excluded PRIMARY ENDPOINT: after administration Increase
in SCr ≥ 0.5 mg/dL from
baseline to 45 to 120 hours 204 evaluable patient 210 evaluable patient Solomon, RJ et. al., Circulation 115, 3189 (2007)
p = 0.39
CARE
p = 0.44
p = 0.15
Gadolinium
Gadolinium chelates used extensively in MR imaging.
Once Considered a potential “substitute” for iodonated RCM in pts with renal insufficiency and anaphylactoid reactions.
Advantages have not been documented and visualization is an issue compared with iodonated RCM.
Nephrotic Systemic Fibrosis (NSF) or Nephrotic Fibrosing Dermopathy (NFD) identified in patients with baseline renal dysfunction following gadolinium.
N-acetylcysteine: a Meta-analysis of 20 Randomized Trials
20 Random Trials, N=2195, CI 95%; Nallamothu BK et al. Am J Med. 2004; 117:938-47
Other Considerations
Carbon Dioxide
Alternative Contrast Agent Used in conjunction with small dose of iodinated contrast Potential Neurotoxicity Recommended only below diagram
Volume: Hydration
Diuretics not of benefit mannitol may be detrimental Sodium Bicarbonate: inconsistent data, unclear benefit 0.9 NS better than 0.5 NS IV better than oral Pre and post hydration preferred, CHF patient dependent.
Rudnick. Prevention of Contrast-induced Nephropathy, 2013
Other Considerations
Hemofiltration and Hemodialysis
Neither can be recommended routinely In Stage 5 CKD, more information is needed
Drugs
Atrial natriuretic peptide Statins Ascorbic Acid Trimetazidine
Renal Guard System Fluid management device that guides fluid replacement.
More information required before routinely recommended.
Recommendations for Decreasing Risk of Contrast Induced Acute Renal Injury/CIN
Manage Medications
Withhold, if clinically appropriate, potentially nephrotoxic drugs including aminoglycoside antibiotics, anti-rejection medications and nonsteroidal anti inflammatory drugs (NSAID).
Manage Intravascular Volume (Avoid Dehydration)
Administer a total of at least 1L of isotonic (normal) saline beginning at least 3 hrs before and continuing at least 6-8 hrs after the procedure.
i. initial infusion rate 100 to 150 ml/hr adjusted post procedure as clinically indicated
Radiographic Contrast Media
Minimize volume Low- or iso-osmolar contrast agents
Post-Procedure: Discharge/Follow-Up
Obtain follow-up SCr 48 hrs post procedure Consider holding appropriate medications until renal function returns to normal, i.e. metformin, NSAID
Final Thoughts
Question
In comparison with the low-osmolar contrast agent iopamidol-370, use of the iso-osmolar contrast agent iodixanol-320 would be expected to result in which of the following outcomes in patients who have moderate to-severe kidney disease and are at high risk for contrast induced acute kidney injury?
(A) No change in injury (B) Increase in injury (C) Decrease in injury
© 2010 ABIM
In comparison with the low-osmolar contrast agent iopamidol-370, use of the iso-osmolar contrast agent iodixanol-320 would be expected to result in which of the following outcomes in patients who have moderate-to-severe kidney disease and are at high risk for contrast-induced acute kidney injury?
(A) No change in injury (B) Increase in injury (C) Decrease in injury
© 2010 ABIM